MIST (Metabolic Intervention With Semaglutide and THR-β Therapy) Trial

NCT07505303 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: EC0011
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 15

Brief Summary

The primary objective of this trial is to evaluate the effect of oral ECC4703 on body weight reduction and in a sub-study on liver fat content as assessed by change in magnetic resonance imaging proton density fat fraction (MRI-PDFF) at Week 20.

Conditions

Adult Obesity; Weight Management

Keywords

Obesity; GLP-1; Weight Management; Semaglutide; MIST; ECC4703; THR-β

Outcome Measures

Primary Outcomes (5)

• Percentage Change in Body Weight from Baseline (Week 9) to Week 20

  Baseline (Week 9) to Week 20

• Proportion of Participants Achieving ≥5% Reduction in Body Weight from Baseline (Week 9) to Week 20

  Baseline (Week 9) to Week 20

• Absolute Change in Liver Fat Content as Measured by MRI-PDFF in Participants With Hepatic Steatosis

  Baseline (Week 9) to Week 20

• Percentage Change in Liver Fat Content as Measured by MRI-PDFF in Participants With Hepatic Steatosis

  Baseline (Week 9) to Week 20

• Proportion of Participants With ≥30% Relative Reduction in Liver Fat Content as Measured by MRI-PDFF

  Baseline (Week 9) to Week 20

Secondary Outcomes (17)

• Change in Percentage Lean Mass as Measured by DXA

  Baseline (Week 9) to Week 20

• Change in Percentage Total Body Fat Mass as Measured by DXA

  Baseline (Week 9) to Week 20

• Change in Percentage Visceral Fat Mass as Measured by DXA

  Baseline (Week 9) to Week 20

• Change in Glycemic Parameters from Baseline (Week 9) to Week 20

  Baseline (Week 9) to Week 20

• Change in Lipid Parameters from Baseline (Week 9) to Week 20

  Baseline (Week 9) to Week 20

Study Arms (2)

Arm 1: ECC4703 + semaglutide

EXPERIMENTAL

ECC4703 orally QD + semaglutide SC once weekly

Drug: ECC4703; Drug: Semaglutide

Arm 2: Placebo + semaglutide

PLACEBO COMPARATOR

Placebo orally QD + semaglutide SC once weekly

Drug: Placebo; Drug: Semaglutide

Interventions

ECC4703 DRUG

orally QD

Arm 1: ECC4703 + semaglutide

Semaglutide DRUG

SC once weekly

Arm 1: ECC4703 + semaglutide; Arm 2: Placebo + semaglutide

Placebo DRUG

orally QD

Arm 2: Placebo + semaglutide

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of providing written informed consent and complying with all trial procedures.
• Willing to comply with contraception requirements (as applicable to males and females of childbearing potential).
• Obese with BMI ≥30 kg/m\^2 and stable body weight within 6 months prior to screening.
• HbA1c ≤6.5%.
• Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m\^2 (per CKD-EPI 2021 formula).
• If participant consents to enter the imaging substudy, has liver fat content by MRI-PDFF \>8% at baseline (Week 9).

You may not qualify if:

• History or current diagnosis of type 1 or type 2 diabetes mellitus.
• Weight change \>5% of total body weight within 6 months prior to screening or planned initiation of a weight loss program or use of weight-altering medication.
• Obesity induced by endocrine disorders such as Cushing's syndrome or monogenic or syndromic obesity such as Prader-Willi syndrome.
• Use of GLP-1 agonist treatment within the last 6 months prior to screening.
• History or current evidence of a pituitary disorder.
• Have current treatment with or history (within 3 months prior to screening) of treatment with medications that may cause significant weight gain.
• ALT or AST \>1.5×ULN, or ALP \>1.5×ULN at screening.
• Documented evidence or clinical signs/symptoms of advanced liver disease including liver cirrhosis, portal hypertension, or hepatic decompensation.
• History of significant alcohol consumption for \>3 consecutive months within a year prior to screening.
• Current or past therapy with THR-β agonists (eg, resmetirom).
• Active untreated hyperthyroidism or hyperthyroidism currently treated with antithyroid medications including methimazole or propylthiouracil.
• Clinically significant thyroid dysfunction including uncontrolled hypothyroidism or hyperthyroidism.
• History of bariatric surgery, fitting of a weight loss device, or intestinal bypass surgery within 5 years prior to screening.
• History of major surgery within 8 weeks prior to screening.
• Clinically relevant acute or chronic medical condition or unstable disease of the cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric, immune or dermatologic system.

Sponsors & Collaborators

• Eccogene: lead

Study Sites (15)

Central Research Associates - Flourish - PPDS

Birmingham, Alabama, 35205, United States

Location

Anaheim Clinical Trials LLC - Anaheim - CenExel - PPDS

Anaheim, California, 92081, United States

Location

Collaborative Neuroscience Network - Los Alamitos- CenExel - PPDS

Los Alamitos, California, 90720, United States

Location

AES - DRS - Optimal Research Florida - Melbourne

Melbourne, Florida, 32934, United States

Location

ForCare Clinical Research - CenExel FCR - PPDS

Tampa, Florida, 33613, United States

Location

Atlanta Center for Medical Research - CenExel ACMR - PPDS

Atlanta, Georgia, 30331, United States

Location

iResearch Atlanta - CenExel - PPDS

Decatur, Georgia, 30030, United States

Location

AES - DRS - Synexus Clinical Research US, Inc. - Richfield - Minneapolis

Richfield, Minnesota, 55423, United States

Location

Velocity Clinical Research (3345 N 107th St) - Omaha - Nebraska - PPDS

Omaha, Nebraska, 68134, United States

Location

Velocity Clinical Research - Durham - PPDS

Durham, North Carolina, 27701, United States

Location

Velocity Clinical Research - Cincinnati (Springdale) - Ohio - PPDS

Cincinnati, Ohio, 45246, United States

Location

Velocity Clinical Research - Providence - PPDS

East Greenwich, Rhode Island, 02818, United States

Location

Velocity Clinical Research - Dallas - PPDS

Dallas, Texas, 75230, United States

Location

AES - DRS - Synexus Clinical Research US, Inc. - San Antonio

San Antonio, Texas, 78229, United States

Location

Flourish Research - San Antonio - PPDS

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Obesity

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Eccogene Clinical Trials

CONTACT

+1-617-807-4087; contact@eccogene.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2026
• First Posted: April 1, 2026
• Study Start: March 13, 2026
• Primary Completion (Estimated): November 20, 2026
• Study Completion (Estimated): November 20, 2026
• Last Updated: April 1, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (15)